A peripheral blood gene expression score is associated with plaque volume and phenotype by intravascular ultrasound with radiofrequency backscatter analysis: results from the ATLANTA study

Abstract

Background: A composite, peripheral gene expression score based on quantitative RNA-measurements has been validated for detecting stenosis against invasive coronary X-ray angiography. IVUS/VH has been validated for quantitative measurements of coronary plaque volume and composition and has been shown to be predictive of outcomes and treatment effects. The correlation between peripheral gene expression and coronary plaque composition by intravascular ultrasound with radiofrequency backscatter (IVUS/VH) is unknown.

Methods: Peripheral blood gene expression score (GES) was prospectively measured in 18 patients undergoing IVUS/VH. Plaque volume and composition [fibrous tissue (FI), fibro-fatty tissue (FF), necrotic core (NC) and dense calcium (DC)] were quantified in 3 dimensions in all plaques within the entire pullback. The relationship to GES was assessed by Spearman rank correlation.

Results: Mean age was 61.1±8.6 years; 67% were male. 1,158 mm of coronary anatomy was imaged by IVUS/VH. Using a validated scale of 1-40, mean GES was 21.6±9.4. GES was associated with plaque volume (R(2)=0.55; P=0.018), NC volume (R(2)=0.56; P=0.015), DC volume (R(2)=0.60; P=0.007), and non-calcified plaque volume (R(2)=0.50; P=0.036) by Spearman rank correlation.

Conclusions: In this preliminary report, increased GES was associated with higher plaque volume and a more vulnerable plaque phenotype as evidenced by NC and DC. This composite GES is not only associated with obstructive coronary disease, but also with higher plaque volume and vulnerable phenotype.

Keywords: Gene expression; intravascular ultrasound; necrotic core; plaque volume; vulnerable plaque.

Figure 1

Plaque composition by intravascular ultrasound with radiofrequency backscatter analysis (IVUS/VH). Grayscale IVUS dataset in longitudinal (A) and cross-sectional views (B) and corresponding IVUS/VH datasets (C,D) are shown; Percent contribution of each IVUS/VH plaque component in current study population (E), presented as mean ± standard deviation (n=18 subjects)

Figure 2

Schematic of segment selection of plaque burden ≥40% for quantitative analysis of intravascular ultrasound with radiofrequency backscatter analysis (IVUS/VH) dataset. The entire vessel pullback from the IVUS/VH dataset was analyzed frame-by-frame in each subject and the minimal lumen area (MLA) frame was selected. The study segment extended proximally and distally from the MLA frame until reaching 3 consecutive frames containing less than 40% plaque burden in each direction

Figure 3

3-Dimensional calculation of plaque burden for study segment. The total vessel and lumen volumes for the study segment were measured. Plaque burden was calculated as the difference between the total vessel and lumen volumes, expressed as a percentage of the total vessel volume

Figure 4

Correlation between gene expression score and intravascular ultrasound with radiofrequency backscatter analysis (IVUS/VH) plaque volumes. IVUS/VH datasets with low plaque volumes [fibrous tissue (FI), fibro-fatty tissue (FF), necrotic core (NC), and dense calcium (DC)] in a subject with a low gene expression score of 5 (A) and high plaque volumes in a subject with a high gene expression score of 34 (B) are shown. Linear regression analyses demonstrate that gene expression score and total plaque volume (R²=0.55; P=0.018), NC volume (R²=0.56; P=0.015), and DC volume (R²=0.60; P=0.007) were significantly correlated, but not after Bonferroni adjustment (C)